Less Liver Cancer in HCV Patients Given Antiviral Therapy

Antiviral therapy may reduce the risk of hepatocellular carcinoma in patients with hepatitis C infections, Dr. Nina Kimer reported in the Oct. 22 issue of BMJ Open, published online.

Moreover, the effect seems to persist regardless of whether sustained virologic response is achieved.

Dr. Kimer, of Copenhagen University Hospital, Hvidovre, Denmark, and colleagues conducted a meta-analysis of trials looking at hepatitis C-related cirrhosis or fibrosis (BMJ Open 2012;2:e001313 [doi:10.1136/bmjopen-2012-001313]).

Courtesy US. Dept of Veterans Affairs

The primary analysis focused on randomized controlled trials, although prospective cohort studies with control groups were included in sensitivity analyses.

The authors searched the Cochrane Library, PubMed, EMBASE, and Web of Science databases, as well as reference lists from relevant papers, conference proceedings, and the World Health Organization Trial Search Portal.

Studies looking at HIV and chronic hepatitis B were excluded, for a total of eight randomized trials and five prospective cohort studies.

The duration of therapy (which included pegylated interferon in two trials, interferon plus ribavirin in one trial, and interferon monotherapy in the remaining trials) varied from 1 to 5 years. Follow-up ranged from 2 to 8.7 years.

Overall, the authors found that 81 of 1,156 patients who received antiviral therapy and 129 of 1,074 control patients who received no therapy developed hepatocellular carcinoma.

The relative risk for antiviral therapy, compared with no treatment, was 0.53 (95% confidence interval, 0.34-0.81).

"The corresponding number needed to treat to prevent one case of [hepatocellular carcinoma] was eight patients," added the researchers.

And while the effect of antivirals was more pronounced among patients with a virological response (RR 0.15; 95% CI, 0.05-0.45), there was nevertheless a clear reduction in risk for nonresponders to antivirals, with a relative risk of 0.57, compared with controls (95% CI 0.37-0.85).

"Although the intervention was more beneficial among sustained virological responders than nonresponders, there was a clear effect in both patient groups. ... Antiviral therapy may have beneficial effects on the risk of developing HCC that are unrelated to the virological response."

On the other hand, there was no reported effect of antiviral therapy on all-cause mortality, liver-related mortality, or liver-related morbidity in this population.

Dr. Kimer conceded several limitations to this analysis. "Only two of the included trials evaluated pegylated interferon, which is the current standard treatment for chronic hepatitis C."

Moreover, the duration of treatment in several included studies was "relatively long, which may increase the proportion of responders."

Finally, Dr. Kimer added that the researchers were unable to perform subgroup analysis to determine which treatment duration or dose is best.

"Based on the duration of follow-up and the lack of clear evidence concerning morbidity or mortality, we cannot exclude that interferon delays rather than prevents carcinogenesis," concluded the investigators.

Nevertheless, the "protection from HCC might be even better among patients in current antiviral therapy since the proportion of virological responders continues to increase with ongoing improvements in therapy," they wrote.

"Additional randomized trials with longer follow-up are still warranted to determine whether this is the case," they noted.

The authors disclosed having no outside funding and no competing interests related to this study.

Antiviral therapy may reduce the risk of hepatocellular carcinoma in patients with hepatitis C infections, Dr. Nina Kimer reported in the Oct. 22 issue of BMJ Open, published online.

Moreover, the effect seems to persist regardless of whether sustained virologic response is achieved.

Dr. Kimer, of Copenhagen University Hospital, Hvidovre, Denmark, and colleagues conducted a meta-analysis of trials looking at hepatitis C-related cirrhosis or fibrosis (BMJ Open 2012;2:e001313 [doi:10.1136/bmjopen-2012-001313]).

Courtesy US. Dept of Veterans Affairs

The primary analysis focused on randomized controlled trials, although prospective cohort studies with control groups were included in sensitivity analyses.

The authors searched the Cochrane Library, PubMed, EMBASE, and Web of Science databases, as well as reference lists from relevant papers, conference proceedings, and the World Health Organization Trial Search Portal.

Studies looking at HIV and chronic hepatitis B were excluded, for a total of eight randomized trials and five prospective cohort studies.

The duration of therapy (which included pegylated interferon in two trials, interferon plus ribavirin in one trial, and interferon monotherapy in the remaining trials) varied from 1 to 5 years. Follow-up ranged from 2 to 8.7 years.

Overall, the authors found that 81 of 1,156 patients who received antiviral therapy and 129 of 1,074 control patients who received no therapy developed hepatocellular carcinoma.

The relative risk for antiviral therapy, compared with no treatment, was 0.53 (95% confidence interval, 0.34-0.81).

"The corresponding number needed to treat to prevent one case of [hepatocellular carcinoma] was eight patients," added the researchers.

And while the effect of antivirals was more pronounced among patients with a virological response (RR 0.15; 95% CI, 0.05-0.45), there was nevertheless a clear reduction in risk for nonresponders to antivirals, with a relative risk of 0.57, compared with controls (95% CI 0.37-0.85).

"Although the intervention was more beneficial among sustained virological responders than nonresponders, there was a clear effect in both patient groups. ... Antiviral therapy may have beneficial effects on the risk of developing HCC that are unrelated to the virological response."

On the other hand, there was no reported effect of antiviral therapy on all-cause mortality, liver-related mortality, or liver-related morbidity in this population.

Dr. Kimer conceded several limitations to this analysis. "Only two of the included trials evaluated pegylated interferon, which is the current standard treatment for chronic hepatitis C."

Moreover, the duration of treatment in several included studies was "relatively long, which may increase the proportion of responders."

Finally, Dr. Kimer added that the researchers were unable to perform subgroup analysis to determine which treatment duration or dose is best.

"Based on the duration of follow-up and the lack of clear evidence concerning morbidity or mortality, we cannot exclude that interferon delays rather than prevents carcinogenesis," concluded the investigators.

Nevertheless, the "protection from HCC might be even better among patients in current antiviral therapy since the proportion of virological responders continues to increase with ongoing improvements in therapy," they wrote.

"Additional randomized trials with longer follow-up are still warranted to determine whether this is the case," they noted.

The authors disclosed having no outside funding and no competing interests related to this study.

Antiviral therapy may reduce the risk of hepatocellular carcinoma in patients with hepatitis C infections, Dr. Nina Kimer reported in the Oct. 22 issue of BMJ Open, published online.

Moreover, the effect seems to persist regardless of whether sustained virologic response is achieved.

Dr. Kimer, of Copenhagen University Hospital, Hvidovre, Denmark, and colleagues conducted a meta-analysis of trials looking at hepatitis C-related cirrhosis or fibrosis (BMJ Open 2012;2:e001313 [doi:10.1136/bmjopen-2012-001313]).

Courtesy US. Dept of Veterans Affairs

The primary analysis focused on randomized controlled trials, although prospective cohort studies with control groups were included in sensitivity analyses.

The authors searched the Cochrane Library, PubMed, EMBASE, and Web of Science databases, as well as reference lists from relevant papers, conference proceedings, and the World Health Organization Trial Search Portal.

Studies looking at HIV and chronic hepatitis B were excluded, for a total of eight randomized trials and five prospective cohort studies.

The duration of therapy (which included pegylated interferon in two trials, interferon plus ribavirin in one trial, and interferon monotherapy in the remaining trials) varied from 1 to 5 years. Follow-up ranged from 2 to 8.7 years.

Overall, the authors found that 81 of 1,156 patients who received antiviral therapy and 129 of 1,074 control patients who received no therapy developed hepatocellular carcinoma.

The relative risk for antiviral therapy, compared with no treatment, was 0.53 (95% confidence interval, 0.34-0.81).

"The corresponding number needed to treat to prevent one case of [hepatocellular carcinoma] was eight patients," added the researchers.

And while the effect of antivirals was more pronounced among patients with a virological response (RR 0.15; 95% CI, 0.05-0.45), there was nevertheless a clear reduction in risk for nonresponders to antivirals, with a relative risk of 0.57, compared with controls (95% CI 0.37-0.85).

"Although the intervention was more beneficial among sustained virological responders than nonresponders, there was a clear effect in both patient groups. ... Antiviral therapy may have beneficial effects on the risk of developing HCC that are unrelated to the virological response."

On the other hand, there was no reported effect of antiviral therapy on all-cause mortality, liver-related mortality, or liver-related morbidity in this population.

Dr. Kimer conceded several limitations to this analysis. "Only two of the included trials evaluated pegylated interferon, which is the current standard treatment for chronic hepatitis C."

Moreover, the duration of treatment in several included studies was "relatively long, which may increase the proportion of responders."

Finally, Dr. Kimer added that the researchers were unable to perform subgroup analysis to determine which treatment duration or dose is best.

"Based on the duration of follow-up and the lack of clear evidence concerning morbidity or mortality, we cannot exclude that interferon delays rather than prevents carcinogenesis," concluded the investigators.

Nevertheless, the "protection from HCC might be even better among patients in current antiviral therapy since the proportion of virological responders continues to increase with ongoing improvements in therapy," they wrote.

"Additional randomized trials with longer follow-up are still warranted to determine whether this is the case," they noted.

The authors disclosed having no outside funding and no competing interests related to this study.